title: Functional interactions between OCA2 and the protein complexes BLOC-1, BLOC-2, and AP-3 inferred from epistatic analyses of mouse coat pigmentation.
abstract: The biogenesis of melanosomes is a multistage process that requires the function of cell-type-specific and ubiquitously expressed proteins. OCA2, the product of the gene defective in oculocutaneous albinism type 2, is a melanosomal membrane protein with restricted expression pattern and a potential role in the trafficking of other proteins to melanosomes. The ubiquitous protein complexes AP-3, BLOC-1, and BLOC-2, which contain as subunits the products of genes defective in various types of Hermansky-Pudlak syndrome, have been likewise implicated in trafficking to melanosomes. We have tested for genetic interactions between mutant alleles causing deficiency in OCA2 (pink-eyed dilution unstable), AP-3 (pearl), BLOC-1 (pallid), and BLOC-2 (cocoa) in C57BL/6J mice. The pallid allele was epistatic to pink-eyed dilution, and the latter behaved as a semi-dominant phenotypic enhancer of cocoa and, to a lesser extent, of pearl. These observations suggest functional links between OCA2 and these three protein complexes involved in melanosome biogenesis.
authors.affiliation: Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
authors.forename: Diego J
authors.initials: DJ
authors.lastname: Hoyle
authors.forename: Imilce A
authors.initials: IA
authors.lastname: Rodriguez-Fernandez
authors.forename: Esteban C
authors.initials: EC
authors.lastname: Dell'angelica
mesh_terms: D016115:Albinism, Oculocutaneous / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D003116:Color; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004843:Epistasis, Genetic; D005260:Female; D006197:Hair / Q000378:metabolism*; D022861:Hermanski-Pudlak Syndrome / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D037102:Lectins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008543:Melanins / Q000378:metabolism; D051379:Mice; D009154:Mutation; D010858:Pigmentation / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D033921:Vesicular Transport Proteins
chemical_list: C513476:Bloc1s6 protein, mouse; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C554282:Hps6 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D037102:Lectins; D008543:Melanins; D014157:Transcription Factors; D033921:Vesicular Transport Proteins; C060759:enhancer-binding protein AP-3